AstraZeneca announces top-line results from Phase III OSKIRA Trials of FOSTAMATINIB and decision not to proceed with regulatory filings

June 04, 2013 -- Rights to the compound will be returned to Rigel Pharmaceuticals
AstraZeneca today announced top-line results from OSKIRA-2 and OSKIRA-3, the
remaining pivotal Phase III clinical trials investigating fostamatinib, the
first oral spleen tyrosine kinase (SYK) inhibitor in development as an oral
treatment for rheumatoid arthritis (RA).

In the OSKIRA-2 study of patients inadequately responding to disease modifying
anti-rheumatic drugs (DMARDs), fostamatinib in combination with DMARDs showed
statistically significant improvements in ACR20 response rates at 24 weeks in
both the 100mg twice daily group and the group receiving 100mg twice daily for
four weeks followed by 150mg once daily (39.6%, p

In the OSKIRA-3 study of patients inadequately responding to methotrexate (MTX)
and a single TNF-alpha antagonist, fostamatinib in combination with MTX showed
statistically significant improvements in ACR20 response rates at 24 weeks in
the 100mg twice daily group (36.2%, p=0.004) but not in the group given 100mg
twice daily for four weeks followed by 150mg once daily (27.8%, p=0.168)
compared to placebo (21.1%).

The safety and tolerability findings for fostamatinib observed in the OSKIRA
Phase III programme were generally consistent with those previously reported in
earlier studies. The most commonly reported adverse events in the OSKIRA
programme include hypertension, diarrhoea, nausea, headache and nasopharyngitis
(common cold).

Based on the totality of results from the OSKIRA Phase III programme, including
the data previously reported from OSKIRA-1, AstraZeneca has decided not to
proceed with regulatory filings for fostamatinib. AstraZeneca will return the
rights to the compound to Rigel Pharmaceuticals which will decide whether it
will continue the ongoing studies and pursue regulatory filings.

Briggs Morrison, MD, Executive Vice President of Global Medicines Development
and Chief Medical Officer, said: “The results of the late stage trials did not
measure up to the promising results we saw earlier in development. We remain
committed to the search for new treatments for patients with rheumatic and
inflammatory diseases with Phase II compounds in rheumatoid arthritis and lupus
and Phase III compounds in gout and psoriasis.”

As a result of this decision, AstraZeneca will incur a pre-tax impairment charge
of approximately $140 million to R&D expense in the second quarter of 2013 for
the intangible assets relating to fostamatinib. Since intangible asset
impairments (except for IS-related intangibles) are excluded from the company’s
Core financial measures, this impairment will have no impact on the company’s
financial guidance for 2013, which is provided on a Core financial measures
basis. As AstraZeneca will continue to incur some Core R&D costs associated with
the completion of ongoing studies for fostamatinib, there is no change to the
company’s guidance that it expects to hold Core operating costs for 2013
(combined Core SG&A and Core R&D) to a slight increase compared with 2012 on a
constant currency basis.

AstraZeneca announced an exclusive worldwide license agreement with Rigel
Pharmaceuticals in February 2010 for the global development and
commercialisation of fostamatinib. AstraZeneca intends to publish a more
detailed analysis of the OSKIRA clinical programme in due course.

About ACR20

The American College of Rheumatology (ACR) score represents a percentage
improvement in symptoms (tenderness and swelling in the joints). 28 joints are
evaluated for tenderness and swelling respectively (prior to taking any required
analgesic that day if possible). To qualify for an ACR20 score, a person with RA
must have at least 20% fewer tender joints and at least 20% fewer swollen
joints. He or she must also show a 20% improvement in at least three of the
following five areas: 1) the person’s overall (global) assessment of his or her
own RA, 2) the physician’s global assessment of the person’s RA, 3) the person’s
assessment of his or her own pain, 4) the person’s assessment of his or her own
physical functioning, and 3) the results of an erythrocyte sedimentation rate or
C-reactive protein blood test (both of which test for inflammation).

About the OSKIRA programme

The (Oral SYK Inhibition in Rheumatoid Arthritis) OSKIRA programme was designed
to investigate fostamatinib as a potential new oral treatment option for
rheumatoid arthritis and an alternative to injectable therapies for patients
with an inadequate response to conventional Disease Modifying Anti-Rheumatic
Drugs (DMARDs), including methotrexate (OSKIRA-1 and OSKIRA-2) and those with an
inadequate response to TNF-a antagonists (OSKIRA-3).

- OSKIRA-1 was a 12-month study with ~900 patients, examining the effect
of fostamatinib (100 mg twice-daily or 100 mg twice-daily for one month followed
by 150 once-daily) compared with placebo over a 24 week period, in patients
responding inadequately to methotrexate. OSKIRA-1 had co-primary endpoints of
ACR20 (composite endpoint assessing signs and symptoms of rheumatoid arthritis)
and mTSS (x-ray endpoint assessing structural progression) at 24 weeks.

- OSKIRA-2 was a 12-month study with ~900 patients, examining the effect
of fostamatinib (100 mg twice-daily or 100 mg twice-daily for one month followed
by 150 once-daily) compared with placebo over a 24 week period, in patients
responding inadequately to DMARDs. OSKIRA-2 had a primary endpoint of ACR20 at
24 weeks.

- OSKIRA-3 was a six-month study of ~320 patients assessing the effect of
fostamatinib (100 mg twice-daily or 100 mg twice-daily for one month followed by
150 once-daily) compared with placebo in patients responding inadequately to TNF
-a antagonist therapy. The primary endpoint of OSKIRA-3 was ACR20 at 24 weeks.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business that
focuses on the discovery, development and commercialisation of prescription
medicines, primarily for the treatment of cardiovascular, metabolic,
respiratory, inflammation, autoimmune, oncology, infection and neuroscience
diseases. AstraZeneca operates in over 100 countries and its innovative
medicines are used by millions of patients worldwide. For more information
please visit: www.astrazeneca.com